We compared cytomegalovirus (CMV)—specific interferon-γ (IFN-γ), interleukin 2 (IL—2), and CD154 CD4⁺ T cell responses of infants to those from chronically infected adults and from children aged 4–5 years. Magnitudes of the responses were similar, although coexpression of IFN-γ plus CD154 occurred more than coexpression of IFN-γ plus IL-2 or IL-2 plus CD154. Responses remained constant during infancy, although the proportion of IFN-γ—producing cells increased from infancy to adulthood. Most responding cells in infants were undifferentiated (i.e., CD27⁺CD28⁺), although IFN-γ—producing cells were disproportionately CD27⁻. By 12 months after diagnosis, viremia was rarely detectable, indicating that CMV was controlled despite the slow development of CMV-specific CD4⁺ T cell responses.